N-6-2-(4-aminophenyl)ethyl-adenosine enhances the anticonvulsive activity of antiepileptic drugs

N-6-2-(4-Aminophenyl)ethyl-adenosine (APNEA, a non-selective agonist of the adenosine A, receptors), at the subprotective dose of 1 mg/kg against electroconvulsions, significantly potentiated the anticonvulsive action of phenobarbital, diphenylhydantoin and valproate against maximal electroshock, bring ineffective at lower doses. APNEA (0.0039-1 mg/kg) also enhanced the protective activity of carbamazepine. Aminophylline (5 mg/kg) and 8-cyclopentyl-1,3-dimethylxanthine (8-CPX, 5 mg/kg), reversed the APNEA (1 mg/kg)-induced enhancement of the anticonvulsive action of phenobarbital, diphenylhydantoin and valproate, but not that of carbamazepine produced by APNEA at 0.0039 mg/kg. The adenosine agonist did not alter the plasma levels of antiepileptic drugs studied, so a pharmacokinetic interaction is not probable. Finally, APT TEA (0.0156 and 1 mg/kg) administered alone or in combination with carbamazepine significantly decreased the body temperature and impaired long-term memory. Our results suggest that APNEA at low doses potentiates the protective activity of carbamazepine most likely through the A(3) subtype of adenosine receptors. At higher doses, APNEA seems to enhance the anticonvulsive effect of other antiepileptics via adenosine A(1) receptors.